Since the metered dose pressurised inhaler was introduced in the mid-1950's, inhalation has become the most widely used route for delivering bronchodilators, offering a rapid onset of action and a low instance of systemic side effects. More recently, inhalation from a pressurised inhaler has been a route selected for the administration of other drugs, e.g., ergotamine, which are not primarily concerned with the treatment of a bronchial malady.
The metered dose inhaler is dependent upon the propulsive force of a propellant system used in its manufacture. The propellant generally comprises a mixture of liquified chlorofluorocarbons (CFC's) which are selected to provide the desired vapour pressure and stability of the formulation. Propellants 11, 12 and 114 are the most widely used propellants in aerosol formulations for inhalation administration.
In recent years it has been established that CFC's react with the ozone layer around the earth and contribute towards its depletion. There has been considerable pressure around the world to reduce substantially the use of CFC's and various Governments have banned the "non-essential" use of CFC's. Such "nonessential" uses include the use of CFC's as refrigerants and blowing agents, but heretofore the use of CFC's in medicines, which contributes to less than 1% of the total use of CFC's, has not been restricted. Nevertheless, in view of the adverse effect of CFC's on the ozone layer it is desirable to seek alternative propellant systems which are suitable for use in inhalation aerosols or an inhaler which is capable of delivering drugs in such an efficacious manner without employing an aerosol propellant.
W092/11050 discloses an inhaler device for dispensing droplets of liquid medicament to a patient comprising a body having a mouth piece or nasal adaptor, and a reservoir of liquid medicament in communication with an aerosol generator, the aerosol generator comprising a chamber for liquid medicament and a nozzle arrangement comprising a plurality of orifices in fluid flow relationship with liquid medicament in said chamber, means for cyclically pressurising the liquid medicament in said chamber such that liquid from said chamber is periodically expelled through the orifices as atomised droplets of liquid medicament so they may be inhaled via the mouth piece or nasal adaptor, the inhaler additionally comprising dosage control means for deactivating the aerosol generator after a predetermined time or after a predetermined volume of liquid medicament has been expelled from the chamber. The cyclic pressurisation may be achieved utilising a piezo-electric element which is caused to vibrate ultrasonically and acts directly or indirectly on the liquid.
In one embodiment of W092/11050 the nozzle assembly is vibrated. The nozzle assembly may be flexible and comprise a piezo-electric element, e.g., in the form of a ring attached to the nozzle array extended around the orifices, such that when the piezo-electric element is excited it causes vibration of the nozzle arrangement at ultrasonic frequencies resulting in cyclic pressurisation of the liquid in the chamber and ejection of droplets of liquid through the orifices.
In a further embodiment of W092/11050 the nozzle assembly is vibrated by a vibrator element comprising a piezo-electric ring secured to a metal disc of larger diameter, the vibrating element having a central aperture through which droplets from the nozzle array are emitted. The vibrating element is preferably secured only over its central portion, either directly to the nozzle array or to the housing of the chamber in close proximity to the nozzle array e.g. over a central portion of about 4 mm diameter, such that ultrasonic energy is transferred directly to the nozzle array. This arrangement allows the outer area of the vibrating element, which is typically about 20 mm diameter, to vibrate freely as a resonator and enables aerosol generation to occur with an input power to the piezo-electric element of about 0.5 W. Also the arrangement has less tendency to draw tiny air bubbles in through the nozzles during operation, since this reduces the tendency for and effects of, vibrational mode hopping which can occur if the piezo driver is attached around its periphery.
During testing such a device, it was discovered that when seepage is allowed to occur to the extent of producing a small drop on the external surface of the nozzle array, subsequent excitation of the piezo transducer does not immediately generate a stream of droplets. Instead, there is a brief delay before atomisation commences while the drop is drawn back into the liquid chamber under the influence of the vibrating nozzles. Furthermore, if the liquid chamber is empty and a drop is deliberately placed on the nozzle array, the same effect is observed: the drop is drawn in through the array and subsequently atomised into primary monodispersed droplets. This phenomenon can be utilised in an alternative construction of an inhaler.